Predicting the timing of maturational spurts in skeletal age

Measures of maturity provide windows into the timing and tempo of childhood growth and maturation. Delayed maturation in a single child, or systemically in a population, can result from either genetic or environmental factors. In terms of the skeleton, delayed maturation may result in short stature or indicate another underlying issue. Thus, prediction of the timing of a maturational spurt is often desirable in order to determine the likelihood that a child will catch up to their chronological age peers. Serial data from the Fels Longitudinal Study were used to predict future skeletal age conditional on current skeletal age and to predict the timing of maturational spurts. For children who were delayed relative to their chronological age peers, the likelihood of catch‐up maturation increased through the average age of onset of puberty and decreased prior to the average age of peak height velocity. For boys, the probability of an imminent maturational spurt was higher for those who were less mature. For girls aged 11 to 13 years, however, this probability was higher for those who were more mature, potentially indicating the presence of a skeletal maturation plateau between multiple spurts. The prediction model, available on the web, is most relevant to children of European ancestry living in the Midwestern US. Our model may also provide insight into the tempo of maturation for children in other populations, but must be applied with caution if those populations are known to have high burdens of environmental stressors not typical of the Midwestern US. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Differential contribution to gene expression prediction of histone modifications at enhancers or promoters

The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.     

The contribution of the C-terminal undecapeptide sequence of urogastrone-epidermal growth factor to its biological action

Progressive enzymic degradation of human urogastrone-epidermal growth factor (URO-EGF) has given a series of fragments shortened at the C-terminus leading to removal of 20% of the structure. These peptides have been evaluated for their ability to bind to polyclonal antiserum and to isolated membrane receptors, to stimulate thymidine uptake by fibroblasts and to inhibit gastric acid secretion in rats. The related molecule human transforming growth factor-alpha, was also assayed and showed similar potency to URO-EGF in all systems. Reduced binding to the receptors of the fragments was paralleled by reduction in both biological activities indicating that this portion of the molecule was concerned entirely with receptor binding. After removal of 11 amino acids from the C-terminus the residue peptide was a full agonist although higher concentrations were necessary.     

Platelet reactivity: a contribution to age dependence studies

The authors examined 230 healthy donors (20-90 years) as to basic biochemical and haematological parameters and those parameters characterizing the function of blood platelets. Besides well known age dependences of fibrinogen concentration, AT III, erythrocyte sedimentation, glucose, cholesterol, alpha-2-macroglobulin and circulating immunocomplexes the results are presented showing a pronounced dependence of primary haemostatic system upon age. Within the age groups 65-75 years and those above 75 years there was a significantly higher amount of circulating aggregates (increase up to 152%), elevated concentration of beta-thromboglobulin and F VIII R:Ag. The increased reactivity of platelets is detectable even by applying relatively simple tests such as the determination of heparin-neutralizing activity, aggregation response to lower concentrations of induces or the determination of the amount of circulating aggregates.     

A contribution to the geographical interpretation of biological change

Geography has traditionally been assigned the role of handmaiden in evolutionary studies. In this work a different understanding of the relationship between biological change and locational setting is developed: evolution as a dynamic form of spatial interaction. In the causal model presented, adaptive change is portrayed as a negative feedback response contributing to a general spatial-temporal process of resource cycle tightening involving exchanges between the two fundamental structural sectors (abiotic and biotic) of the earth's surface system. As such, it is rejected as evolution per se. This position makes it possible to circumvent the adaptation yields adaptation circularity, and to view locational circumstances as being evolutionarily causal, yet not deterministic with respect to population-level change. A parallel interpretation of the relation between range and range change and evolution is also implicit; the individualistic hypothesis is thereby superceded by a model of community evolution allowing for individualistic rates of population (adaptive and) range change, but operating on the principle that populations should tend to change range in common directions (as a response to spatially-varying degrees of efficiency of turnover of resources vital to biotic sector function). This in turn leads to the possibility of normative biogeographic modelling. Comment is also made on the relationship of the present understanding to disequilibrium and dynamic equilibrium interpretations of evolutionary change, and to human cultural evolution.     

Bone marrow contribution to skeletal muscle: a physiological response to stress

Adult bone marrow-derived stem cells (BMDC) have been shown to contribute to numerous tissues after transplantation into a new host. However, whether the participation of these cells is part of the normal response to injury remains a matter of debate. Using parabiotically joined pairs of genetically labeled and wildtype mice, we show here that irradiation-induced damage of the target tissue, injection of bone marrow into the circulation, and immunological perturbation that are consequences of bone marrow transplantation are not necessary for bone marrow contribution to myofibers. Moreover, severe toxin-induced damage is not a prerequisite, as BMDC contribution to muscle is enhanced in response to increased muscle activity resulting from muscle overloading or forced exercise. Indeed, these two forms of muscle stress result in much more rapid contribution (within 1 month) than voluntary running (6 months). These results indicate that BMDC contribute to myofibers in response to physiologic stresses encountered by healthy organisms throughout life.     

To age or not to age

According to the antagonistic pleiotropy theory of ageing, natural selection has favoured genes conferring short-term benefits to the organism at the cost of deterioration in later life. The 'disposable soma' theory expresses this as a life-history strategy in which somatic maintenance is below the level required to prevent ageing, thus enabling higher immediate fertility. It has been argued that a non-ageing strategy will always be bettered by a low but non-zero rate of ageing, because the costs of such ageing will be felt only in the distant future when they are of negligible importance. Here, we examine this argument critically. We find that a non-ageing strategy will be locally optimal if, in the presence of ageing, the onset of deterioration is sufficiently rapid or early. Conversely, ageing will be optimal if deterioration is sufficiently slow or late. As the temporal profile of ageing changes from one of steady deterioration to one involving a sudden loss of vitality after a period of little or no decline, the conditions for a non-ageing strategy to be locally optimal become progressively more stringent. But for all forms of profile considered, conditions can be found for which a strategy involving no ageing is locally optimal.     

Bone marrow cryopreservation: biological aspects

Ten bone marrow suspensions have been cryopreserved by a Programmed Freezer Planer R 201. Total cellularity, viability, differential myelograms, cytochemical pattern and CFU-GM growth "in vitro", have been evaluated on the cellular suspensions both before and after 1 and 18 months of storage in liquid nitrogen. Total cellular recovery and viable cell recovery were satisfactory, cellular loss being due, almost entirely to death of the more mature cells. NASDA reaction did not vary after freezing, on the contrary peroxidase reaction and overall PAS reaction showed respectively a slight and an almost complete disappearance. LAP reaction was not valuable, after freezing, because of the more mature myeloid cell loss. CFU-GM recovery was satisfactory and clusters and colonies growth in methylcellulose appeared quite similar before and after 1 and 18 months of storage at very low temperature. Our cryopreservation technique cannot prevent some cellular loss or some qualitative cellular damage, but colonizing ability is almost completely preserved.     

Bone material properties and mineral matrix contributions to fracture risk or age in women and men

The strength of bone is related to its mass and geometry, but also to the physical properties of the tissue itself. Bone tissue is composed primarily of collagen and mineral, each of which changes with age, and each of which can be affected by pharmaceutical treatments designed to prevent or reverse the loss of bone. With age, there is a decrease in collagen content, which is associated with an increased mean tissue mineralization, but there is no difference in cross-link levels compared to younger adult bone. In osteoporosis, however, there is a decrease in the reducible collagen cross-links without an alteration in collagen concentration; this would tend to increase bone fragility. In older people, the mean tissue age (MTA) increases, causing the tissue to become more highly mineralized. The increased bone turnover following menopause may reduce global MTA, and would reduce overall tissue mineralization. Bone strength and toughness are positively correlated to bone mineral content, but when bone tissue becomes too highly mineralized, it tends to become brittle. This reduces its toughness, and makes it more prone to fracture from repeated loads and accumulated microcracking. Most approved pharmaceutical treatments for osteoporosis suppress bone turnover, increasing MTA and mineralization of the tissue. This might have either or both of two effects. It could increase bone volume from refilling of the remodeling space, reducing the risk for fracture. Alternatively, the increased MTA could increase the propensity to develop microcracks, and reduce the toughness of bone, making it more likely to fracture. There may also be changes in the morphology of the mineral crystals that could affect the homogeneity of the tissue and impact mechanical properties. These changes might have large positive or negative effects on fracture incidence, and could contribute to the paradox that both large and small increases in density have about the same effect on fracture risk. Bone mineral density measured by DXA does not discriminate between density differences caused by volume changes, and those caused by changes in mineralization. As such, it does not entirely reflect material property changes in aging or osteoporotic bone that contribute to bone's risk for fracture.     

The ovariectomized ewe: its contribution to controlled breeding

The ovariectomized ewe has been used to establish principles and procedures which have proved invaluable in controlled breeding in entire animals. Bioassays in the ovariectomized ewe, the end-point of oestrous behaviour, have been used to identify potent and rapidly metabolized progestagens which were subsequently used to control the time of oestrus and ovulation in cyclic ewes effectively, and to induce oestrus and ovulation in anoestrous ewes. Steroid hormone treatment of the ovariectomized ewe has been used to study relationships between the ovary and the pituitary-hypothalamic axis, to examine transport of embryos within the female tract and to establish the steroid hormone requirements of early pregnancy.